Parvoviruses are small, DNA-containing viruses that infect a variety of animal species. Several parvoviruses are recognized as important causes of disease in animals such as canine parvovirus and feline panleukopenia virus, but parvovirus B19 is the only strain that is pathogenic in humans. Parvovirus B19 is a member of the genus Parvovirus in the family Parvoviridae. The mammalian parvoviruses are very species specific. B19 does not infect other animals, and animal parvoviruses do not infect humans. Human Parvovirus B19 occurs endemically worldwide. It causes epidemics in small areas, especially affecting kindergartens and schools. Parvovirus B19 infection is generally a self-limiting childhood disease. For example, it was proved that Parvovirus B19 to be the cause of a benign self-limiting childhood exanthema (fifth disease or erythema infectiosum (EI)). However, infection with parvovirus can be dangerous, for example, causing aplastic anemia and/or fetal death in certain groups, e.g., patients with sickle cell anemia. Persistent Parvovirus B19 infection can also cause chronic arthropathies. In immunodeficient patients, parvovirus infection can result in chronic anemia. Parvovirus B19 is also an important cause of nonimmune hydrops fetalis. (Hibbs J. and Young N., Infectious Diseases 912 (Hoeprich D. et al. eds., J. B. Loppincon Co., Philadelphia, 5th ed, 1994)). There may also be a direct effect of the virus on myocardial tissue (Nelson's Textbook of Pediatrics 15th Ed. 1996).
Laboratory tests for the diagnosis of B19 infection are not available routinely. Diagnosis of EI is usually based on clinical observation of the typical rash and exclusion of other conditions. The virus cannot be isolated by culture. In evaluation of suspected Parvovirus B19 infections, a complete blood cell count and blood chemistry profile are useful in addition to thorough history taking and physical examination (Marshal et al., Postgraduate medicine. 95(8): 165-168, 1994). However, diagnosis of acute and past infection of Parvovirus B19 is based on detection of IgM and IgG antibodies (Pickering et al., Clin. and Diag. Virol. 9(1): 57-63, 1998). Studies of Cassinotti, et al. demonstrated the prevalence of IgG anti-Parvovirus B19 antibodies in patients with various forms of arthritis (Cassinoti et al., Annals of Rheumatic Disease. 54(6): 498-500, 1995). Others have studied the serological profiles and/or prevalence for human Parvovirus B19 in patients with fibromyalgia (FM) (Branco et al., Infeccao viral e fibromyalgia. 7(6): 337-341, 1994), AIDS, and other infections (Mudde et al., Allergy. 50: 193-199, 1995). Recombinant versions of Parvovirus B19 viral capsid proteins VP1 and VP2 have been used as antigens for immunodiagnostic assays, including either IgM or IgG enzyme immunoassays (EIA), immunofluorescence assays (IFA), or Western blot assays, for detection of antiviral antibodies (Kerr et al, J Med Virol. 57(2): 179-185, 1999).
IgE antibodies have been identified in studies of virus other than parvovirus, e.g., IgE anti-parainfluenza virus (Welliver et al., J. Pediatrics. 101(6): 889-896, 1982) and IgE anti-respiratory syncytial virus (RSV) (Welliver et al., New England J. of Med. 305(15): 841-846, 1981; Russi et al., J. Clin. Microbiol. 31: 819-823, 1993) in sera from pediatric patients (Welliver et al., 1982). However, IgE anti-RSV-F(a) and IgE anti-RSV-G(a) antibodies were not detected in nasal washes and sera from infants (De Alarcon et al., J. Pediatrics. 138(3): 311-7, 2001).
Previous studies have also identified the presence and function of IgE anti-HIV antibodies in the serum of a subset of HIV-1 seropositive, nonprogressor pediatric patients, who remained relatively healthy, despite decreased numbers of peripheral blood CD4+ T cells (Secord et al., J. Allergy Clin Immunol. 98(5): 979-984, 1996; Pellegrino et al., AIDS Research and Human Retroviruses 18(5):367-76, 2002).
It is well known that immunological factors play an important role in virus pathogenesis (Clerici et al., Immunol Today. 107: 14-20, 1993). For example, patients chronically infected with Hepatitis C Virus (HCV) exhibit immune dysfunction with a Th2-dominant cytokine profile, while Th1 cytokines are prominent in those with self-limited HCV infection (Sauerbruch et al., C. J. Hepatol. 31: 971-976, 1999; Tsai et al., Hepatology. 25: 449-457, 1997). Both Th1 and cytotoxic T lymphocyte (“CTL”) responses have been reported to play a crucial role in recovery from HCV infection (Missale et al, J. Clin, Invest. 98: 706-715, 1996; Chang et al., C. J. Immunol. 162: 1156-1163, 1999). Furthermore, in HIV-1 disease, the loss of the Th1 response has been correlated with disease progression and loss of protective cellular immunity (Walker et al., AIDS. 4: 177-184, 1990). Similar studies, in HIV-1 disease, have shown a persistence of HIV-1 specific IgE after 210 days, and retained its ability to suppress HIV-1 production in vitro (Pellegrino et al.). Further, it has been demonstrated that specific IgE anti-HIV-1 antibodies can protect a subject against HIV-1 disease progression by promoting cytotoxic responses or by suppressing virus production (Secord et al.; Pellegrino et al.; Seroogy et al., J. All. Clin. Immunol. 104: 1045-1051, 1999).
It was demonstrated that the low affinity receptor for IgE, CD23, can be proteolytically cleaved from surfaces of CD23 expressing cells into biologically active soluble fragments, some of which retain the ability to bind IgE (Dugas et al., Euro. Cytokine Network. 3:35-41, 1992). It has also been shown that CD23 (membrane bound and soluble forms) increases production of IgE by B cells through interacting with CD21 on B cell surfaces (Bonnefoy et al., Int. Arch Allergy Immunol. 104: 40-42, 1995; Bonnefoy et al., Immunol. Today. 12: 41S-420, 1996). The increase in CD23 may also serve to regulate selective IgE responses. See, e.g., Delespesse et al., Immunol. Rev. 125: 77-97, 1992, as well as provide an initial anti-viral response, as demonstrated in parasitic infection. See, e.g., Capron et al., Science. 264: 1876-1877, 1994; Vouldoukis et al., Proc. Natl. Acad. Set 92: 7804-7808, 1995.
Functions of CD23 include specific regulation of IgE production, IgE-mediated cytotoxicity and release of mediators, IgE-depenjdent antigen focusing, and promotion of B cell growth (Fujiwara et al., Proc Nat. Acad. Sci USA. 91(15): 6835-6839, 1994). CD23 has also been shown to increase on monocytes in AIDS (Miller et al., AIDS Research and Human Retroviruses 17:443-52, 2001). In addition, CD23+ expression by peripheral blood leukocytes (“PBL”) has been evaluated in diseases such as rheumatoid arthritis (RA) (Fernandez-Gutierrez et al., Clin Immunol Immunopathol. 72(3): 321-327, 1994) and HIV-1 (Larcher et al, J. Acq. Immune Def. Syn. 3: 103-108, 1990). However, later studies found decreased numbers of CD23+ B cells (Larcher et al; Rodriguez et al., Clin. Immunol and Immunopath. 81: 191-199, 1996), and increased numbers of CD23+ T cells (Carini et al., Proc. Nat. Acad. Set USA 85: 9214-9218, 1988; Carini et al, Int Arch. Allergy Appl. Immunol. 88: 116-118, 1989) in HIV-1.
Further, studies of Imani, et al., have shown that infection with MMR vaccine can induce IgE class switching in a human B cell line and freshly prepared PBL (Imani et al, Clin. Immunol. 100(3): 355-61, 2001). It has also been implicated that an IgE bounds to its Fc receptor as an (APC) Antigen Presenting Cell in atopy (Mudde et al.).
Previous serology studies, through ELISA methodology, have identified IgM (in early stage of infection) and IgG (chronic presence in a patient) antibodies, but not IgE antibodies, specific against Parvovirus B19 antigens. Moreover, the level of total IgG or IgM in healthy people and in parvovirus infected patients does not have diagnostically significant difference. Therefore, an immunoglobulin specific for Parvovirus B19, such as an antibody, which is only detectable in parvovirus infected patients but not detectable in healthy people, would have diagnostic and/or prognostic implications to facilitate the early detection of parvoviral infection thereby permitting early intervention to treat or prevent the deleterious effects of Parvovirus infection.